Chronic cocaine induces long-lasting neuro-adaptations within the mesocorticolimbic reward pathways (the motivational circuit) that are thought to underlie the manifestation of addictive behaviors. Recently, brain-derived neurotrophic factor (BDNF), within the NAcc and the ventral tegmental area (VTA), has emerged as a modulator of cocaine reward and reinstatement (Grimm et al. 2003; Hall et al. 2003; Horger et al, 1999; Lu et al. 2004). The cortico-striatal pathway from the prefrontal cortex (PFC) to the NAcc is critical in the manifestation of relapse behavior (Kalivas 2004; McFarland et al. 2003), and less is known about the role of BDNF neuro-transmission in this pathway following chronic cocaine. In the present study we will first examine BDNF protein expression within the motivational circuit following withdrawal from cocaine self-administration. Secondly, we will manipulate PFC neurotransmission by infusing BDNF directly into the PFC. We will then evaluate the enduring effects of intra-PFC BDNF infusions on reinstatement testing, TrkB receptor cell surface expression, and the phosphorylation state of the TrkB receptor, ERK, AKT, and PLCg, in the motivational circuit.